Spray Freeze Drying in a Fluidized Bed at Normal and Low Pressure

The aim of this study is to develop the spray freeze drying process and its hardware and to investigate its capabilities to dry thermosensible substances such as pharma-proteins at normal and low pressures. As the result, the spray freeze fluidized–bed dryer was constructed. During the study, the drying kinetic comparison between classical and spray freeze–drying technologies was done. Spray freeze drying has shown short process times and allows advanced control, product particle shape and size uniformity, and high solubility. This shows that the fluidized-bed freeze-drying process could be an alternative for classical freeze-drying processes. Identified problems are the low yield of the primary drying phase and the strong electrostatic effects during the secondary drying step. However, the innovative process has shown an excellent capability to dry and stabilize the thermosensitive substances, such as pharma-proteins.     

Cracking during freeze-drying in dense freeze cast ceramics: Role of drying rate

Cracks can form during the freeze-drying of freeze cast ceramic suspensions while attempting to produce dense ceramics. The suspensions contain alumina particles dispersed in cyclohexane. The rate of drying is controlled by the pressure and temperature during drying (slow drying at atmospheric pressure and −15°C and fast drying under vacuum while the temperature slowly increases from −80°C to room temperature). X-Ray micro-computed tomography was used to characterize internal crack formation. Cracks were found to occur during freeze-drying rather than during freezing. Both slow and fast drying produced cracks, although two different morphologies were observed. Mechanistic models are proposed for the formation of both types of cracks. The rate of freezing was found to influence the formation of cracks. Slow freezing tended to reduce the formation of drying cracks because the slower freezing produced a more heterogeneous distribution of particles and porous regions, which tends to allow stress to be relieved by opening up existing pores rather than forming cracks in the more homogeneous fast frozen bodies.     

Optimal Control of the Primary Drying Stage of Freeze Drying of Solutions in Vials Using Variational Calculus

Abstract

The problem of operating freeze drying of pharmaceutical products in vials placed in trays of a freeze dryer to remove free water (in frozen state) at a minimum time was formulated as an optimal control problem. Two different types of freeze dryer designs were considered. In type I freeze dryer design, upper and lower plate temperatures were controlled together, while in type II freeze dryer design, upper and lower plate temperatures were controlled independently. The heat input to the material being dried and the drying chamber pressure were considered as control variables. Constraints were placed on the system state variables by the melting and scorch temperatures during primary drying stage. Necessary conditions of optimality for the primary drying stage of freeze drying process in vials are derived and presented. Furthermore, an approach for constructing the optimal control policies that would minimize the drying time for the primary drying stage was given. In order to analyze optimal control policy for the primary drying stage of the freeze-drying process in vials, a rigorous multi-dimensional unsteady state mathematical model was used. The theoretical approach presented in this work was applied in the freeze drying of skim milk. Significant reductions in the drying times of primary drying stage of freeze drying process in vials were obtained, as compared to the drying times obtained from conventional operational policies.     

A Novel Data Preprocessing Method for the Modeling and Prediction of Freeze-Drying Behavior of Apples: Multiple Output–Dependent Data Scaling (MODDS)

In the present study, the freeze drying behavior of apples have been modeled and predicted. Because freeze-drying is a very expensive and complex process, modeling of the freeze-drying process is a challenging task. In this study, a novel data scaling method called multiple output–dependent data scaling (MODDS) has been proposed and combined with an adaptive neuro-fuzzy inference system (ANFIS) to forecast the moisture content (MC), moisture ratio (MR), and drying rate (DR) values, which are outputs of freeze-drying behavior of apples. The input parameters of the freeze drying system are the sample thicknesses, drying time, pressure, relative humidity, chamber temperature, and sample temperature. Using the input parameters, the outputs of the freeze-drying process of apples were predicted using a hybrid system based on MODDS and ANFIS. In the first stage, only input parameters were scaled using MODDS. In the second stage, the outputs of freeze drying of apples were predicted with the scaled input parameters using ANFIS algorithm. Ninety-two samples were included in the data set, including 10-, 7-, and 5-mm samples. In order to evaluate the performance of the proposed model, the mean absolute error (MAE), mean square error (MSE), root mean square error (RMSE), coefficient of determination (R ²), index of agreement (IA), and mean absolute percentage error (MAPE) were used. Though MSE values of 2.48, 0.035, and 0.011 and IA values of 0.887, 0.887, and 0.466 were obtained for MC, MR, and DR, respectively, using the ANFIS prediction algorithm the hybrid MODDS-ANFIS model achieved MSE values of 0.003, 0.00005, and 0.00007 and IA values of 0.999, 0.999, and 0.993 for the prediction of MC, MR, and DR, respectively. The results obtained demonstrate that the proposed hybrid system is a robust and efficient method for the modeling and prediction of freeze-drying behavior of apples.     

Spray Freeze Drying in a Fluidized Bed at Normal and Low Pressure

The aim of this study is to develop the spray freeze drying process and its hardware and to investigate its capabilities to dry thermosensible substances such as pharma-proteins at normal and low pressures. As the result, the spray freeze fluidized-bed dryer was constructed. During the study, the drying kinetic comparison between classical and spray freeze-drying technologies was done. Spray freeze drying has shown short process times and allows advanced control, product particle shape and size uniformity, and high solubility. This shows that the fluidized-bed freeze-drying process could be an alternative for classical freeze-drying processes. Identified problems are the low yield of the primary drying phase and the strong electrostatic effects during the secondary drying step. However, the innovative process has shown an excellent capability to dry and stabilize the thermosensitive substances, such as pharma-proteins.     

Optimal Control of the Primary Drying Stage of Freeze Drying of Solutions in Vials Using Variational Calculus

The problem of operating freeze drying of pharmaceutical products in vials placed in trays of a freeze dryer to remove free water (in frozen state) at a minimum time was formulated as an optimal control problem. Two different types of freeze dryer designs were considered. In type I freeze dryer design, upper and lower plate temperatures were controlled together, while in type II freeze dryer design, upper and lower plate temperatures were controlled independently. The heat input to the material being dried and the drying chamber pressure were considered as control variables. Constraints were placed on the system state variables by the melting and scorch temperatures during primary drying stage. Necessary conditions of optimality for the primary drying stage of freeze drying process in vials are derived and presented. Furthermore, an approach for constructing the optimal control policies that would minimize the drying time for the primary drying stage was given. In order to analyze optimal control policy for the primary drying stage of the freeze-drying process in vials, a rigorous multi-dimensional unsteady state mathematical model was used. The theoretical approach presented in this work was applied in the freeze drying of skim milk. Significant reductions in the drying times of primary drying stage of freeze drying process in vials were obtained, as compared to the drying times obtained from conventional operational policies.     

黑加仑真空冷冻与微波真空联合干燥工艺研究

以黑加仑为原料,对其进行了真空冷冻与微波真空联合干燥工艺的研究。结果表明：先真空冷冻后微波真空干燥（FDMV）的组合方式是可行的;联合干燥合理工艺参数为：微波功率1．34kW。绝对压力11kPa,转换含水率为20％（wb）;通过试验验证,联合干燥生产的脱水黑加仑的感官品质和营养成分接近真空冷冻干燥,联合干燥方式对节省干燥时间和降低能耗是有效的。     

构建微波冷冻干燥质扩散系数的一种新方法

针对现有微波冷冻干燥模型中必须依靠实验以确定扩散系数的问题．提出一种构建扩散系的新方法。根据毛细管低压气体输运理论，利用物料本身的细微结构、气体分子平均自由程、气体状态参数和气体物性参数来构建扩散系数，在此基础上建立微波冷冻干燥模型。并结合牛肉的微波冷冻干燥行模型可靠性分析。结果表明，新建模型能够很好地描述微波冷冻干燥过程温度场的变化及其特征．升过程干燥曲线的理论值与实验值之间的相对误差小于10％。     

Drying of shiitake mushroom by combining freeze-drying and mid-infrared radiation

Mid-infrared drying (MIRD) was applied before or after freeze-drying (FD) of shiitake mushroom to shorten the drying time, to enhance the rehydration, and to better preserve the aroma compounds and color. The effect of application of MIRD before freeze drying (MIRD–FD) and after freeze drying (FD–MIRD) on drying time, color, rehydration ratio, apparent density, microstructure and aroma compounds was measured, explained and compared with the effect of FD on these parameters. The results showed that the combination of FD (for 4 h) followed by MIRD saves 48% time compared to FD while keeping the product quality at an acceptable level. The MIRD–FD combination was found to be inferior compared to the FD–MIRD as the former tended to produce products with a collapsed surface layer and poor rehydration capability. The combination of MIRD with FD had a significant effect on aroma retention and caused an increase of sulfur compounds such as dimethyl, trisulfide and 1,2,4-trithiolane.     

奶粉的喷雾冷冻干燥研究

研究开发了实现喷雾冷冻干燥工艺的装置,并以奶粉为物料,进行了试验研究。结果表明,料液可以在-40～-30℃实现快速冷冻,且采用该喷雾冷冻干燥装置可将干燥时间从原来真空冷冻干燥的48h缩短为10h。最后,对获得的干燥产品进行了粉体形态的测试和分析。     

Infrared-Assisted Freeze Drying of Tiger Prawn: Parameter Optimization and Quality Assessment

This article presents an extensive experimental study coupled with statistical analysis on infrared (IR)-assisted freeze drying of tiger prawn (Penaeus monodon) in cuboidal geometry. The work aims to estimate quality attributes of freeze-dried prawn in terms of final product temperature (below protein denaturation temperature), rehydration ratio, and final moisture content as a function of process parameters, viz. IR temperature (55–65°C), distance between sample and IR heater (30–60 mm), sample thickness (10–25 mm) and freeze-drying time (5.5–6.5 h). Response surface methodology (RSM) has been employed using a three-parameter, three-level face-centered central composite design (FCCD) to develop multivariate regression models in order to evaluate the influence of process parameters on the quality of the freeze-dried prawn. Optimal drying conditions of 10-mm sample thickness, 60-mm sample distance from the IR heater, 65°C IR temperature, and freeze-drying time of 6.37 h have been established. Separate validation experiments at the derived optimal conditions ascertained the predictive ability of the developed model equations. The outcome of this study would contribute to the development of technical capabilities for the design of freeze dryers applicable to such high-valued foodstuffs.     

Effect of Cryoprotectant and Freeze-Drying Process on the Stability of W/O/W Emulsions

In order to protect a hydrophilic drug and to prolong its further delivery, the formulation of multiple emulsions could be worthy. However, the double emulsions are not stable, their structure can change, leading to the formation of a single emulsion as the destruction of the system, and the drug can release easily from the globules in liquid state. The freeze-drying technology could be used to produce dry emulsion, the powder form being much more stable. The aim of this work was to study the influence of a cryoprotectant and a freeze-drying process on the stability of W/O/W emulsions. Samples were frozen at two different freezing rate (ν _f  = 0.55°C/min and 1.25°C/min) and successively dried at two different sublimation temperature (T _s  = ? 10°C and ? 20°C). The particle size distributions were measured by granulometer and UV spectrophotometer was performed to investigate the leakage of internal constituent. The glass transition temperature (T _g ) of the double emulsions was analyzed by DSC. The particle sizes became even smaller after freeze drying, except when κ-carrageenan is used as a cryoprotectant. In that case, the particles became aggregated after freeze drying, whatever the process conditions. The mean size is considerably reduced when the globules are diluted at low concentration in glucose and trehalose solution. When the concentration is increased, the size distribution is not significantly affected. The leakage of the internal aqueous phase to the external one during freeze drying was measured as an indicator of the structure stability. It is affected by the nature of the cryoprotectant and the conditions of the freeze-drying process. The leakage of the internal phase was smaller when cycle III (ν _f  = 1.25°C/min, T _s  = ? 10°C) was processed. From our experiments, we suppose that the water transfer from the inner phase to the outer aqueous phase results in the diminution of the globules size in double emulsion. The T _g of the double emulsions diluted with trehalose and glucose were determined at ? 33.8°C and ? 47.1°C. In contrast, the T _g of double emulsion with κ-carrageenan and HES did not appear.     

Physicothermal Properties of Freeze-Dried Fish Oil Nanocapsules Frozen under Different Conditions

This research compared the effects of vacuum freeze drying (VFD) and conventional freeze drying (CFD) processes on the stability of fish oil–loaded nanocapsules (NCs). For CFD, the NCs showed aggregation that was dependent on the freezing temperature. The encapsulation efficiency of CFD was greater than that of VFD, except at the freezing temperature of ?30°C. From differential scanning calorimetry (DSC) analysis and scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images, it was concluded that the CFD process was more effective in the oxidative stability of the fish oil–loaded NCs. In addition, the vacuum-freezing process may affect the fragility of the poly-?-caprolactone membrane due to its low encapsulation efficiency and aggregation of particles. No differences in Z-potential values between the CFD samples were observed, whereas in the VFD samples, it became increased in the negative charge when decreasing the cooling temperature of the fish oil–loaded nanocapsules for the freeze-drying procedure. Regarding the observation of surface tension, CFD samples presented lower values than VFD samples at given freezing temperature.     

Microwave Freeze Drying of Sea Cucumber Coated with Nanoscale Silver

To develop an improved dehydration method for sea cucumber, microwave freeze drying was tested as a potential method. According to our experimental results, microwave freeze drying can reduce drying time to about half of the traditional vacuum freeze-drying process. To ensure a high degree of sterilization, a novel nanoscale silver coating technique was combined with microwave freeze drying. Microwave freeze drying combined with nanoscale silver coating treatment leads to a much lower microorganism number with no significant effect on drying efficiency and sensory quality.     

Microwave Freeze Drying of Sea Cucumber Coated with Nanoscale Silver

To develop an improved dehydration method for sea cucumber, microwave freeze drying was tested as a potential method. According to our experimental results, microwave freeze drying can reduce drying time to about half of the traditional vacuum freeze-drying process. To ensure a high degree of sterilization, a novel nanoscale silver coating technique was combined with microwave freeze drying. Microwave freeze drying combined with nanoscale silver coating treatment leads to a much lower microorganism number with no significant effect on drying efficiency and sensory quality.     

Role of Freeze Drying in Nanotechnology

Governments worldwide have spent more money on nanotechnology between 1997 and 2005 than on the Apollo project. The spending trend is still going upwards. Drying is an indispensable operation in the fabrication of nanosized materials. Hence, it is no surprise to find a large number of papers published in the past decade on drying and nano-related materials. This article reviews the literature and highlights the opportunities and challenges of freeze drying in nanotechnology. Freeze drying has found application in the production of nanoparticles for electrochemical, environmental, engineered materials, and pharmaceutical industries. The retention of the homogenous properties typically found in a solution, the small size of particles produced, and the long shelf life obtained for pharmaceutical applications are the primary reasons for choosing freeze drying. The relatively cheap operation cost compared to supercritical fluid extraction is another reason. Freezing was found to be a very important step in obtaining desired particle size and properties. Primary drying of solvent sublimation should be carried out at a temperature below the collapse temperature. Cryoprotectants are frequently necessary in preserving the original properties of active pharmaceutical ingredients. Spray freezing into liquid was found to be an optimal operation in order to minimize the air–liquid interfacial loss of bioactivity. A continuous freeze-drying process for production of granules of nanoparticles would be in demand, a dream that freeze-drying researchers have had for over a decade. This freeze drying may be carried out under vacuum or at atmospheric pressure using proper gases.     

Influence of inner vapor transfer property of a freeze dryer on the design space of drying process

A freeze dryer with a radiative heating device was constructed and the inner vapor transfer property was regulated by separating the drying chamber and the condenser with an orifice. A mathematical model was used to obtain the contour diagrams of the selected parameters (e.g., product temperature and total drying period) during drying as a function of the heating condition and chamber pressure. Furthermore, the inner vapor transfer coefficients of the freeze dryer were used to draw the operation lines on the diagrams. The combinations of contour diagrams and operation lines clearly depict the design spaces. It was confirmed that the inner vapor transfer property substantially affected the acceptable operation range, and it was revealed that this coefficient is key to quantify the performance of a freeze dryer. This coefficient could also be used to predict the occurrence of choked flow during a freeze-drying run.     

Studies on the Microwave Freeze Drying Technique and Sterilization Characteristics of Cabbage

The vacuum freeze-drying (FD) technique used in the food industry can yield a high-quality product, but it is very expensive and requires a long processing time. Besides, the quantity of microorganisms in FD products can often exceed the required standard. As a result, it will be important to develop a new freeze-drying technique. In this article, cabbage was used as a model material, and the microwave field was used as a heat source to supply sublimation heat so that the drying time was shortened greatly. The effect of the microwave sterilization during the drying process was evaluated. Effects of the pressure, thickness of material being dried, and the input microwave power on such indices as drying time and the microorganism number were studied. Compared with the method of ordinary freeze drying, microwave freeze drying (MFD) can greatly reduce the drying time and has a notable sterilization effect.     

Studies on the Microwave Freeze Drying Technique and Sterilization Characteristics of Cabbage

The vacuum freeze-drying (FD) technique used in the food industry can yield a high-quality product, but it is very expensive and requires a long processing time. Besides, the quantity of microorganisms in FD products can often exceed the required standard. As a result, it will be important to develop a new freeze-drying technique. In this article, cabbage was used as a model material, and the microwave field was used as a heat source to supply sublimation heat so that the drying time was shortened greatly. The effect of the microwave sterilization during the drying process was evaluated. Effects of the pressure, thickness of material being dried, and the input microwave power on such indices as drying time and the microorganism number were studied. Compared with the method of ordinary freeze drying, microwave freeze drying (MFD) can greatly reduce the drying time and has a notable sterilization effect.     

Ice-mould freeze casting of porous ceramic components

Porous, hollow ceramic components were produced by freeze casting technique. For this purpose aqueous slurries with high solid contents were prepared which were stable against freezing down to at least −5 °C. Ice cores were made by coating steel components with freezing water which were subsequently dip-coated with the ceramic suspensions. After freeze drying which removes both, the ice core and the frozen suspension liquid, and sintering, ceramic components with a high amount of open porosity including steel parts could be achieved. As an example hydroxyapatite was used for showing the opportunities of the freeze casting technology among others for applications in the field of bone replacement. The influence of the solid content of the hydroxyapatite slurries on the ice crystal growth has been investigated by means of compact hydroxyapatite bodies which were prepared by freeze casting using ice moulds with cylindrical cavities.